Letters in Organic Chemistry - Current Issue

Herein, the influence of structural attributes, including the interactions of lipases with support systems, substrates, products/byproducts, and the media environment, on enzyme stability, selectivity and activity are discussed. Substrates/products, such as methanol, glycerol, phenolic acids and polyphenols, can inhibit lipase activity by influencing the mass flow of the reactants and products or by enzyme denaturation, which is also caused by extreme pH, high temperatures, and digestive action of most organic solvents. Immobilization techniques that involve chemical bonding between the functional groups of the support and the amino acids of the lipase maintain the enzyme’s active conformation via the formation of stable secondary structures. Functionalized metal nanoparticles and metal and covalent organic frameworks (COFs and MOFs) covalently bond to lipases, reducing the reliance of the active site conformation on hydrogen bonding and disulfide bonds. The crystallinity of COF- and MOF-immobilized lipases allows them to be used in contrasting media environments and at high temperatures, which increases the reaction kinetics and improves the catalytic yield. On the other hand, inert support systems such as silica promote catalytic yields by minimizing protein leaching, which fairly maintains the amount of the preloaded lipase. The structure of substrates also plays a large role, whereas some lipases strictly prefer narrow substrates others such as Candida species lipases are liberal and allow substrates of varying bulkiness/steric hindrances.

The synthesis of 3,5-disubstituted pyrazolines, integrated with heterocyclic systems, represents a crucial area of chemical research due to their pharmacological and biological significance. This article reviews various synthetic methods used to prepare 3,5-disubstituted pyrazolines with different heterocyclic groups. The methodology employed in this study entails a multi-step synthesis, where readily available starting materials are transformed into complex pyrazoline derivatives through strategic reaction sequences. Incorporating heterocyclic systems not only enhances the structural diversity but also imparts unique chemical and biological properties to these compounds. Various heterocyclic groups, such as furans, thiophenes, and pyridines, are introduced at the 3,5-positions of the pyrazoline ring, yielding a versatile library of compounds. This study highlights the potential applications of these novel compounds in medicinal chemistry and drug discovery, emphasizing their bioactivity against specific targets. Preliminary data suggests that certain derivatives possess promising pharmacological activities, making them potential candidates for further development as therapeutic agents. In summary, this review provides a valuable contribution to the field of organic synthesis, offering a novel and efficient route to synthesize 3,5-disubstituted pyrazolines with heterocyclic systems. Furthermore, the structural activity relationship of the compounds is also discussed. The structural diversity and potential pharmacological properties of these compounds make them valuable candidates for further exploration and development in drug discovery and related areas.

In this study, DFT calculations were performed in order to identify the reaction products of the photochemical dimerization of indones. Calculations allowed us to assume that all tested reactions occurred in the first excited singlet state. The irradiation of 2-phenyl-5-nitroindone gave the main product, the anti-cis head-to-tail dimer, while the other two compounds found in the experiments were the syn-cis head-to-head dimer and the anti-cis head-to-tail dimer. The irradiation of 2-phenylindone gave the main product, syn-cis-head-to-tail dimer, while the minor products were anti-cis-head-to-tail and anti-cis-head-to-head dimer. The photochemical dimerization of 2-methyl-3-phenylindone gave the main product, anti-cis-head-to-tail dimer, while the minor component of the mixture was syn-cis-head-to-head dimer.

A general and efficient multi-component reaction has been established for the construction of 5-amino tetrazoles and guanidines under mild reaction conditions. All the substrates are readily carried out under optimized reaction conditions to provide their respective target products in good to excellent yields. The regioselectivity of the reaction is also explained in this manuscript. Further, this method is free, uses water as a green solvent, and is practical (at room temperature and under an open atmosphere). In addition, we could not identify any other products during the reaction procedure. Phenyltetrazoleamines are readily converted into their C-N cross-coupled products in good to high yield under mild reaction conditions.

In recent years, numerous methods have been developed for the synthesis of coumarins via Pechmann reaction catalyzed by various catalysts. Although each of the synthetic strategies previously reported has its own merit, most of these methods are associated with certain disadvantages, including the use of commercially unavailable metal catalysts and organic solvents, low yields, and long reaction times. Therefore, the development of a highly efficient, green, and sustainable catalytic methodology for the synthesis of coumarins is still desirable. Humic acid has been found to be an efficient catalyst for the synthesis of coumarins via the Pechmann reaction at 80°C under solvent-free conditions. The methodology enables the synthesis of structurally diverse coumarins from phenols and β-keto esters within 5-8 min in high yields (91-99%). The green, commercially available, inexpensive organocatalyst can be effectively recycled and reused five times with no significant drop-down in the yield of the product. The method reported has the advantages of high yield, no need for metal catalysts, short reaction time, simple operation, and green and reusable catalyst.

A rapid and direct route for the new synthesis of various quinazolines-4 (1H)-ones with appropriate yields through a three-component reaction consisting of the amine-trichloroacetonitrile adduct and isatoic anhydride is a remarkable achievement in organic chemistry. The use of CuO as the catalyst in DMF under reflux conditions at 110°C for 4 hours offers reaction conditions, which are conducive to the formation of the desired products while maintaining good selectivity. The simplicity of the one-pot synthesis and using the available raw materials contribute to the ease of purification of the synthesized quinazolines-4 (1H)-ones, streamlining the overall synthetic process. The synthesized product is often found in drugs and other bioactive molecules.

In this work, 2,3,4-tri-O-acetyl-D-glucurono-6,1-lactone has been prepared from glucuronic acid in two steps by converting it into glucuronic anhydride. In the presence of a catalytic amount of Ce(OTf)3 (10 examples) in ethyl acetate, the glucuronic anhydride provided 6.1-lactone in good to excellent yields. This lactone was used to prepare the novel glycoconjugates of peptidic fragments of arenastatin A, a sponge cytotoxic depsipeptide, and its analogues.

Fused pyrrole, pyridine with pyridinone components are known to possess many biological and pharmaceutical properties. Fused pyrrole with naptharidinone also has many potentials. A tandem approach of intramolecular lactamization and N-arylation using a copper catalyst to obtain a fused pyrrolo-naptharidinone has been developed. A ligand-free method has been proposed for cyclization and Ullmann (C-N coupling) type reaction in a single step. This approach will make it possible to synthesise pyrrolo-naphthyridinone N-aryl substituted natural product compounds without the need for extra additives.

Hydrazo compounds have displayed significant roles in both biological and physical aspects, such as spinamycin as a potent growth inhibitor against fungi and rat sarcoma cells, hydrazo tocopherol as a component of vitamin E, and electron-rich hydrazo-linked triazines as energetic materials. In this study, a metal-free approach was proposed for the synthesis of hydrazo-linked 5-(4-aryl)-1H-1,2,4-triazoles. The methods for the synthesis of 5-(4-aryl)-1H-1,2,4-triazoles initiated by the reaction of aldehyde with semicarbazide. The resulted compound, 5-(4-aryl)-1H-1,2,4-triazol-3-ol, upon reaction with phosphorous oxychloride yielded 3-chloro-5-(4-aryl)-1H-1,2,4-triazoles. These synthesized compounds upon fusión with various aryl and hetero aryl substituted hydrazines provided desired hydrazo moieties. Synthesized hydrazo compounds were characterized by spectroscopic techniques, viz.¹H-NMR, FT-IR and mass spectrometry. In this study, a series of novel hydrazo-linked 5-(4-aryl)-1H-1,2,4-triazoles were synthesized. The methodology proposed in this study eliminates the use of complicated procedures and heavy metals.